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INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.

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INTRODUCTION: Professional identity formation (PIF) is recognized worldwide as an outcome of medical education grounded in the psychology of adult development and the literature on medical professionalism. However, instruments to assess and support PIF are scarce. The Professional Identity Essay (PIE) is an open-ended question assessment of PIF that elicits short narrative responses from learners and that can be analyzed to provide formative feedback and an overall stage of development. In this study, our aim was to translate and adapt the PIE to Brazilian Portuguese. METHODS: We followed a systematic procedure for the translation and cross-cultural adaptation of the instrument. A pilot study was conducted with medical students from the University of São Paulo. After providing individual formative feedback, we administered an online questionnaire to the Brazilian students to better understand the consequences of using the PIE. Content analyses of qualitative data were performed, we employ manifest content analysis, and the categories of analysis emerged from the participants' speeches. RESULTS: Students found the instrument's questions easy to interpret and self-reflective. It also gave students the opportunity to consider their PIF. The PIE was perceived as reliable and brought more awareness of the students' own processes in addition to a sense of capability to foster their own development. In the same way, the students emphasized the importance of being helped in this process. CONCLUSION: We found sufficient evidence of the validity of the PIE in terms of content, face validity, and consequences of use. The PIE enhances self-assurance in PIF through formative assessment and is sensitive to different cultures, making it a potential tool for educators.

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INTRODUCTION: Uncertainty tolerance (UT) is attracting increasing attention in medical education due to the numerous challenges associated with uncertainty in professional life. Inconsistencies in analysing the relationship between UT and moderators may arise from inadequate measurement methods. Most instruments were formulated before the most widely accepted framework was published. Our aim was to investigate the validity of an UT scale using an actual framework to corroborate with better and accurate instruments. METHODS: A total of 1052 students were invited. Various psychometric methods were used to explore validity of the TAMSAD scale in light of actual framework. Classic exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed. Secondly, content item classification was triangulated with exploratory graph analysis (EGA), and the new EFA, CFA, and cognitive diagnostic modelling (CDM) analysis were conducted. The reliability was calculated using Cronbach's alpha and McDonald's omega. RESULTS: A total of 694 students (65.9%) responded to the questionnaire. The reliability of the TAMSAD scale was 0.782. The initial EFA revealed no clear interpretable dimensions. The TAMSAD scale items can be classified into sources of uncertainty. The EGA has three dimensions, and the new EFA led to a 17-item TAMSAD scale with the following three dimensions: ambiguity, complexity, and probability. These dimensions lead to better adjustment fit indices in the new CFA and CDM analyses. CONCLUSION: We found evidence that the TAMSAD scale can be considered a multidimensional scale, organised in terms of sources of uncertainty.

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BACKGROUND: Cleaning workers represent a significant proportion of the active population worldwide, with poor remuneration, particularly in developing countries. Despite this, they remain a relatively poorly studied occupational group. They are constantly exposed to agents that can cause symptoms and respiratory problems. This study aimed to evaluate upper airway inflammation in professional cleaning workers in three different occupational settings by comparing nasal cytology inflammation and clinical profiles. METHODS: We performed a cross-sectional study on the prevalence of upper airway inflammation and symptoms of asthma/rhinitis related to cleaning work, according to workplace. A total of 167 participants were divided into four groups: hospital, university, housekeeper and control. A nasal swab was collected for upper airway inflammation evaluation. Clinical profiles and respiratory symptom employee evaluations were performed using specific questionnaires (European Community Respiratory Health Survey-ECRS and the International Study of Asthma and Allergies in Childhood-ISAAC). RESULTS: Cleaning workers showed increased neutrophils and lymphocytes; the hospital and university groups showed increased macrophages compared to the housekeeper and control groups. The hospital and housekeeper groups showed increased eosinophils when they performed cleaning services for up to one year and reported having more asthma symptoms than the control group. Cleaning workers showed increased rhinitis symptoms. The university group showed increased rhinitis symptoms aggravated by the workplace compared with the hospital and housekeeper groups. Cleaning workers showed an increased affirmative response when directly asked about rhinitis symptoms compared to the control group. CONCLUSIONS: Cleaning workers showed airway inflammation, asthma symptoms and rhinitis, regardless of the occupational environment to which they were exposed, as well as showed increased rhinitis and asthma symptoms. Hospital cleaning workers showed increased macrophages, lymphocytes and eosinophils compared to the others. The length of time spent performing cleaning work was not related to nasal inflammation or respiratory symptoms in this population. However, there were differences in workplaces. Registered on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT03311048. Registration date: 10.16.2017. Retrospectively registered.

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INTRODUCTION: Although the major alterations associated with asthma are related to the airways, there is also evidence of the importance of peribronchial vascular inflammation and remodeling in its pathophysiology. OBJECTIVES: To determine the effects of anti-IL-17 therapy on peribronchial vessels of an asthma model exacerbated by lipopolysaccharide. METHODS: We evaluated several factors, including lung function, inflammation, oxidative stress, vascular remodeling, and signaling pathways present in the peribronchial vessels of 66 male BALB/c mice exposed to ovalbumin and treated (or not) treated with anti-IL-17. Twenty-four hours before the end of the experimental protocol, groups of sensitized animals (OVA-LPS and OVA-LPS anti-IL-17) also received LPS. RESULTS: The OVA-LPS-anti-IL-17 group presented a decrease in several factors [airway resistance and elastance, bronchoalveolar lavage fluid (BALF) cell counts, inflammatory response, eosinophils, TSLP, IL-33, TARC, TNF-α, CD4+, CD8+, IL-4, IL-6, IL-10, IL-17, and VEGF positive cells/104µm2, peribronchovascular edema, and angiogenesis], including remodeling (MMP-9, MMP-12, TIMP-1 and TGF-ß positive cells and volume fraction of collagen fibers I, collagen fibers III, collagen fibers V, decorin, lumican, actin, biglycan, fibronectin, and integrin), oxidative stress (iNOS positive cells and volume fraction of PGF2α), and signaling pathways (FoxP3), as well as dendritic cells, NF-kB, ROCK-1, ROCK-2, STAT-1, and phosphor-STAT1-positive cells compared to OVA-LPS (p < 0.05). CONCLUSIONS: In this model of LPS-induced asthma exacerbation, IL-17 inhibition represents a promising therapeutic strategy, indicating the potential of bronchial vascular control of Th2 and Th17 responses and the activation of the remodeling and oxidative stress pathways, associated with the control of signaling pathways.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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BACKGROUND: Asthma is a disease with reversible bronchoconstriction; however, some patients develop fixed airflow obstruction (FAO). Previous studies have reported the incidence and risk factors of FAO in adults; however, the corresponding factors in children remain poorly understood. AIM: To evaluate the incidence and risk factors of FAO in children and adolescents with asthma. METHOD: Observational and prospective cohort study with a 4-year follow-up of clinically stable patients with asthma (from 6-8 years old). Anthropometric data, history of asthma, number of hospitalizations, frequent exacerbations, asthma severity, asthma control, inhaled corticosteroid dose, atopy, and lung function were analyzed as potential risk factors for FAO. FAO was defined by a ratio of the forced expiratory volume in the first second to the forced vital capacity below the lower limit of normal, even after inhaled and oral corticosteroid treatment. RESULTS: Four hundred and twenty-eight patients were recruited, and 358 were analyzed. The FAO incidence in children and adolescents with asthma was 9.5% (n = 34), starting at 10 years of age. Age, body mass index, hospitalizations for asthma, bronchodilator response, frequent exacerbations, length of exacerbations, and asthma severity were associated with FAO. Frequent exacerbations (odds ratio [OR] = 4.0; 95% confidence interval [CI] = 1.3-11.7) and asthma severity categorized as steps 4 to 5 (OR = 3.5; 95% CI = 1.6-7.6) remained risk factors. CONCLUSIONS: Frequent exacerbations and asthma severity are the risk factors for FAO in children and adolescents with asthma.

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Obese adults with asthma are more likely to develop dynamic hyperinflation (DH) and expiratory flow limitation (EFL) than nonobese asthmatics, and weight-loss seems to improve the breathing mechanics during exercise. However, studies evaluating the effect of weight loss on DH in obese adults with asthma have not been performed. We sought to evaluate the effect of a weight loss program on DH in obese adults with asthma. Forty-two asthma patients were enrolled in a weight loss program (diet, psychological support, and exercise) and were subsequently divided into two groups according to the percentage of weight loss: a ≥5% group ( n = 19) and a <5% group ( n = 23). Before and after the intervention, DH and EFL (constant load exercise), health-related quality of life (HRQoL), asthma control, quadriceps muscle strength and endurance, body composition, and lung function were assessed. Both groups exhibited a decrease of ≥10% in inspiratory capacity (DH) before intervention, and only the ≥5% group showed clinical improvement in DH compared with the <5% group postintervention (-9.1 ± 14.5% vs. -12.5 ± 13.5%, respectively). In addition, the ≥5% group displayed a significant delay in the onset of both DH and EFL and a clinically significant improvement in HRQoL and asthma control. Furthermore, a correlation was observed between reduced waist circumference and increased inspiratory capacity ( r = -0.45, P = 0.05) in the ≥5% group. In conclusion, a weight-loss of ≥5% of the body weight improves DH, which is associated with waist circumference in obese adults with asthma. In addition, the group with greater weight-loss showed a delayed onset of DH and EFL during exercise and improved asthma clinical control and HRQoL. NEW & NOTEWORTHY This is the first study to evaluate dynamic hyperinflation (DH) after a weight loss program in obese patients with asthma. Our results demonstrate that moderate weight loss can improve DH in obese patients with asthma that is associated with a decrease in abdominal fat. Moreover, a minimum of 5% in weight loss delays the onset of DH and expiratory flow limitation besides inducing a clinical improvement in asthma quality of life and clinical control.

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BACKGROUND: The present study aimed to analyze the effects of physical training on an antioxidant canonical pathway and metalloproteinases activity in diaphragm muscle in a model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). METHODS: Male mice were randomized into control, smoke, exercise, and exercise + smoke groups, which were maintained in trial period of 24 weeks. Gene expression of kelch-like ECH-associated protein 1; nuclear factor erythroid-2 like 2; and heme-oxygenase1 by polymerase chain reaction was performed. Metalloproteinases 2 and 9 activities were analyzed by zymography. Exercise capacity was evaluated by treadmill exercise test before and after the protocol. RESULTS: Aerobic training inhibited diaphragm muscle wasting induced by cigarette smoke exposure. This inhibition was associated with improved aerobic capacity in those animals that were submitted to 24 weeks of aerobic training, when compared to the control and smoke groups, which were not submitted to training. The aerobic training also downregulated the increase of matrix metalloproteinases (MMP-2 and MMP-9) and upregulated antioxidant genes, such as nuclear factor erythroid-2 like 2 (NRF2) and heme-oxygenase1 (HMOX1), in exercise + smoke group compared to smoke group. CONCLUSIONS: Treadmill aerobic training protects diaphragm muscle wasting induced by cigarette smoke exposure involving upregulation of antioxidant genes and downregulation of matrix metalloproteinases.

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BACKGROUND: The inverse relationship between exercise capacity and its variation over time and both cardiovascular and all-cause mortality suggests the existence of an etiological nexus between cardiometabolic diseases and the molecular regulators of exercise capacity. Coordinated adaptive responses elicited by physical training enhance exercise performance and metabolic efficiency and possibly mediate the health benefits of physical exercise. In contrast, impaired expression of genes involved in mitochondrial biogenesis or protein turnover in skeletal muscle-key biological processes involved in adaptation to physical training-leads to insulin resistance and obesity. Ingestion of fructose has been shown to suppress the exercise-induced GLUT4 response in rat skeletal muscle. To evaluate in greater detail how fructose ingestion might blunt the benefits of physical training, we investigated the effects of fructose ingestion on exercise induction of genes that participate in regulation of mitochondrial biogenesis and protein turnover in rat's skeletal muscle. METHODS: Eight-week-old Wistar rats were randomly assigned to sedentary (C), exercise (treadmill running)-only (E), fructose-only (F), and fructose + exercise (FE) groups and treated accordingly for 8 weeks. Blood and quadriceps femoris were collected for biochemistry, serum insulin, and gene expression analysis. Expression of genes involved in regulation of mitochondrial biogenesis and autophagy, GLUT4, and ubiquitin E3 ligases MuRF-1, and MAFbx/Atrogin-1 were assayed with quantitative real-time polymerase chain reaction. RESULTS: Aerobic training improved exercise capacity in both E and FE groups. A main effect of fructose ingestion on body weight and fasting serum triglyceride concentration was detected. Fructose ingestion impaired the expression of PGC-1α, FNDC5, NR4A3, GLUT4, Atg9, Lamp2, Ctsl, Murf-1, and MAFBx/Atrogin-1 in skeletal muscle of both sedentary and exercised animals while expression of Errα and Pparδ was impaired only in exercised rats. CONCLUSIONS: Our results show that fructose ingestion impairs the expression of genes involved in biological processes relevant to exercise-induced remodeling of skeletal muscle. This might provide novel insight on how a dietary factor contributes to the genesis of disorders of glucose metabolism.